{"doi":"10.1189/jlb.2ab0314-145r","title":"The<i>Cebpa</i>+37-kb enhancer directs transgene expression to myeloid progenitors and to long-term hematopoietic stem cells","abstract":"<jats:title>Abstract</jats:title><jats:p>C/EBPα is expressed preferentially in myeloid compared with lymphoid or erythroid cells and directs myeloid lineage specification. C/EBPα is also expressed at lower levels in HSCs and in several nonhematopoietic tissues. The Cebpa gene has a conserved, 450-bp segment at +37 kb that harbors enhancer-specific epigenetic marks and is activate in a myeloid cell line. Herein, we characterize transgenic C57BL/6 mice, in which the Cebpa enhancer and 845-bp promoter regulate a hCD4 reporter. FACS analysis, in vitro colony assays, and in vivo competitive and secondary transplantation revealed that myeloid but not MEPs or lymphoid progenitors and also functional LT-HSCs are found almost exclusively in the Cebpa-hCD4+ compared with hCD4− marrow population. hCD4+ CMP yielded predominantly myeloid, whereas hCD4− CMP generated mainly Meg/E colonies. Providing insight into control of CMP maturation, Cebpa and Pu.1 RNAs were preferentially expressed in hCD4+ CMP, Scl, Gata2, Gata1, Klf1, Ets1, and Fli1 predominated in hCD4− CMP, and Runx1, Myb, HoxA9, and Erg levels were similar in both. Cebpa-hCD4 transgene expression was lacking in multiple nonhematopoietic tissues. In summary, the +37-kb Cebpa enhancer and promoter are sufficient for marrow myeloid progenitor and LT-HSC-specific expression.</jats:p>","journal":"Journal of Leukocyte Biology","year":2014,"id":588809,"datarank":0.8939195841566794,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"self_citation_contribution":0.47670807455219194,"citation_network_contribution":0.41721150960448744,"self_endowment_contribution":0.47670807455219194,"citer_contribution":0.41721150960448744,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":15,"citers_with_citation_signal":14,"citers_with_endowment":14,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1182224,"name":"Ou Ma","orcid":"0000-0003-2727-1997","position":1,"is_corresponding":false},{"id":1506440,"name":"Alan D Friedman","orcid":null,"position":2,"is_corresponding":false},{"id":728949,"name":"Hong Guo","orcid":"0000-0002-4015-419X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The<i>Cebpa</i>+37-kb enhancer directs transgene expression to myeloid progenitors and to long-term hematopoietic stem cells","abstract":"<jats:title>Abstract</jats:title><jats:p>C/EBPα is expressed preferentially in myeloid compared with lymphoid or erythroid cells and directs myeloid lineage specification. C/EBPα is also expressed at lower levels in HSCs and in several nonhematopoietic tissues. The Cebpa gene has a conserved, 450-bp segment at +37 kb that harbors enhancer-specific epigenetic marks and is activate in a myeloid cell line. Herein, we characterize transgenic C57BL/6 mice, in which the Cebpa enhancer and 845-bp promoter regulate a hCD4 reporter. FACS analysis, in vitro colony assays, and in vivo competitive and secondary transplantation revealed that myeloid but not MEPs or lymphoid progenitors and also functional LT-HSCs are found almost exclusively in the Cebpa-hCD4+ compared with hCD4− marrow population. hCD4+ CMP yielded predominantly myeloid, whereas hCD4− CMP generated mainly Meg/E colonies. Providing insight into control of CMP maturation, Cebpa and Pu.1 RNAs were preferentially expressed in hCD4+ CMP, Scl, Gata2, Gata1, Klf1, Ets1, and Fli1 predominated in hCD4− CMP, and Runx1, Myb, HoxA9, and Erg levels were similar in both. Cebpa-hCD4 transgene expression was lacking in multiple nonhematopoietic tissues. In summary, the +37-kb Cebpa enhancer and promoter are sufficient for marrow myeloid progenitor and LT-HSC-specific expression.</jats:p>","is_dataset_classified":null,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24868087","pmcid":"PMC4138201","openalex_id":"https://openalex.org/W1994001465","authors":[],"funders":[{"funder_name":"U.S. National Institutes of Health","grant_id":"U01 HL099775","title":null},{"funder_name":"U.S. National Institutes of Health","grant_id":"R01 HL089176","title":null},{"funder_name":"Giant Food Children&apos;s Cancer Research Fund","grant_id":"","title":null}],"total_grants":3,"fwci":2.1052,"citation_percentile":0.86970111,"influential_citations":0,"citation_trend":[{"year":2015,"count":6},{"year":2016,"count":3},{"year":2017,"count":2},{"year":2018,"count":3},{"year":2019,"count":3},{"year":2020,"count":2},{"year":2023,"count":3},{"year":2024,"count":1}],"oa_status":"bronze","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1189/jlb.2AB0314-145R","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1189/jlb.2AB0314-145R","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1189%2Fjlb.2AB0314-145R","host_type":"publisher"},{"url":"https://academic.oup.com/jleukbio/article-pdf/96/3/419/49583377/jlb0419.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1189/jlb.2ab0314-145r","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/24868087","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4138201","host_type":"repository"}],"fields_of_study":["Acute Myeloid Leukemia Research","Epigenetics and DNA Methylation","RNA Research and Splicing","Animals","Bone Marrow Transplantation","CCAAT-Enhancer-Binding Proteins","CD4 Antigens","Cell Lineage","Cell Separation","Colony-Forming Units Assay","Enhancer Elements, Genetic","Flow Cytometry","Gene Expression Regulation","Genes, Reporter","Hematopoietic Stem Cells","Humans","Lymphocytes","Lymphopoiesis","Mice, Inbred C57BL","Mice, Transgenic","Myeloid Cells","Myelopoiesis","Peptide Fragments","Promoter Regions, Genetic","Radiation Chimera","Recombinant Fusion Proteins","Transgenes"],"mesh_terms":["Animals","Cell Separation","Colony-Forming Units Assay","Enhancer Elements, Genetic","Flow Cytometry","Gene Expression Regulation","Hematopoietic Stem Cells","Humans","Lymphocytes","Mice, Inbred C57BL","Mice, Transgenic","Peptide Fragments","Promoter Regions, Genetic","Radiation Chimera","Recombinant Fusion Proteins","CD4 Antigens","Bone Marrow Transplantation","Genes, Reporter","Cell Lineage","Transgenes","Myeloid Cells","CCAAT-Enhancer-Binding Proteins","Lymphopoiesis","Myelopoiesis"],"keywords":["CEBPA","Biology","Myeloid","Haematopoiesis","Enhancer","Cancer research","Myelopoiesis","Transgene","Molecular biology","Progenitor cell","Cell biology","Stem cell","Gene expression","Transcription factor","Genetics","Gene","Differentiation","Hematopoiesis"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-22T22:00:55.669190Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}